title: Postoperative analgesia by intra-articular neostigmine in patients undergoing knee arthroscopy.
abstract: BACKGROUND
  Recently, the spinal administration of neostigmine was shown to produce a dose-dependent analgesia. However, this analgesia is limited by adverse effects. The purpose of this study was to examine the analgesic action of peripheral muscarinic receptors by administering intra-articular neostigmine after operation in patients undergoing knee arthroscopy.
  
  
  METHODS
  Sixty patients (classified as American Society of Anesthesiologists status I or II) having arthroscopic meniscus repair during general anesthesia were randomized to receive, in a double-blind manner, after operation 125, 250, or 500 microg intra-articular neostigmine; 2 mg intra-articular morphine; or as control groups intra-articular saline or 500 microg neostigmine given subcutaneously (s.c.). Visual analog pain scores (VAS), duration of analgesia as defined by first demand for patient-controlled analgesia by morphine, and subsequent 48-h consumption of morphine were evaluated.
  
  
  RESULTS
  Intra-articular (500 microg) neostigmine resulted in significant VAS reduction 1 h after injection compared with patients given intra-articular saline and with those given intra-articular morphine. Analgesia lasted longer after 500 microg intra-articular neostigmine (350 +/- 126 min) compared with intra-articular morphine (196 +/- 138 min; P < 0.05) or with the control groups (intra-articular saline, 51 +/- 11 min; s.c. neostigmine, 46 +/- 8 min; P < 0.05). The need for supplementary analgesia was significantly higher in control groups than for patients given intra-articular morphine or 500 microg intra-articular neostigmine. No significant analgesic effects were observed for the two lower doses of intra-articular neostigmine. Among all study groups, no adverse effects were observed.
  
  
  CONCLUSIONS
  Intra-articular injection of the acetylcholinesterase inhibitor neostigmine produced a moderate but significant analgesic effect. Several mechanisms such as the hyperpolarization of neurons, reduction in the release of pronociceptive neurotransmitters, or activation of the nitric oxide-cyclic guanosine monophosphate pathway might mediate this peripheral cholinergic antinociception by elevating endogenous acetylcholine.
authors.affiliation: Chang Gung Memorial Hospital, Kaohsiung Hsien, Taiwan, Republic of China.
authors.forename: L C
authors.initials: LC
authors.lastname: Yang
authors.forename: L M
authors.initials: LM
authors.lastname: Chen
authors.forename: C J
authors.initials: CJ
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Buerkle
mesh_terms: D000328:Adult; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D001182:Arthroscopy; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007717:Knee / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D009388:Neostigmine / Q000008:administration & dosage*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D011976:Receptors, Muscarinic / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D002800:Cholinesterase Inhibitors; D011976:Receptors, Muscarinic; D009388:Neostigmine; D009020:Morphine